Kostaive (Zapomeran)

What Is Kostaive and What Is It Used For?

Kostaive represents a significant advancement in vaccine technology as the world’s first approved self-amplifying messenger RNA (sa-mRNA) vaccine. Developed by Arcturus Therapeutics in collaboration with CSL Seqirus, it was first approved in Japan by the Ministry of Health, Labour and Welfare in November 2023, followed by European Commission authorisation in February 2025 (EU license number EU/1/24/1873/001), and Medicines and Healthcare products Regulatory Agency (MHRA) approval in the United Kingdom in January 2026.

The vaccine is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2 in individuals aged 18 years and older. It can be used both for primary vaccination in individuals who have not previously been vaccinated against COVID-19, and as a booster dose in individuals who have previously received any authorised COVID-19 vaccine. The decision to use Kostaive should be in accordance with official national recommendations on COVID-19 vaccination.

What distinguishes Kostaive from earlier-generation mRNA vaccines such as Comirnaty (Pfizer-BioNTech) and Spikevax (Moderna) is its self-amplifying mechanism. Conventional mRNA vaccines deliver a fixed amount of mRNA that is translated once into protein before being degraded. In contrast, the sa-mRNA in Kostaive encodes not only the target antigen – the prefusion-stabilised SARS-CoV-2 spike glycoprotein (G clade, D614G variant) – but also a replicase enzyme derived from the Venezuelan equine encephalitis virus (VEEV) replicon. This replicase creates additional copies of the spike protein mRNA within the cell, effectively amplifying the immune-stimulating signal.

This self-amplifying approach has several important practical implications. Because the mRNA multiplies inside cells, a much lower initial dose is needed to achieve a robust immune response. Each dose of Kostaive contains just 5 micrograms of zapomeran, compared to 30 micrograms for the Pfizer-BioNTech vaccine or 50–100 micrograms for the Moderna vaccine. The lower dose may contribute to a reduction in certain systemic side effects, while still inducing strong humoral (antibody) and cellular (T-cell) immunity against SARS-CoV-2.

The mRNA in Kostaive is encapsulated in Arcturus’ proprietary LUNAR (Lipid-enabled and Unlocked Nucleomonomer Agent modified RNA) lipid nanoparticle technology, which protects the fragile mRNA molecule and facilitates its delivery into host cells after intramuscular injection. Once inside the cell, the lipid nanoparticle releases the sa-mRNA, which is then translated by the cell’s ribosomes into both the spike protein and the replicase enzyme. The spike protein is displayed on the cell surface, where it is recognised by the immune system, triggering the production of neutralising antibodies and SARS-CoV-2-specific T cells.

What Should You Know Before Receiving Kostaive?

Contraindications

Kostaive must not be administered to individuals with a known hypersensitivity to the active substance zapomeran or to any of the excipients listed in the product formulation. This includes the lipid components of the LUNAR lipid nanoparticle system. If you have previously experienced an anaphylactic reaction to a prior dose of Kostaive, you must not receive further doses.

Hypersensitivity to any vaccine component is a standard contraindication for all vaccines. Before vaccination, healthcare providers should screen recipients for any history of severe allergic reactions to vaccines or injectable therapies. The excipients in Kostaive include tromethamine (Tris), tromethamine hydrochloride, sucrose, sodium chloride, and lipid components. If you have a known allergy to any of these substances, inform your healthcare provider before vaccination.

Warnings and Precautions

Before receiving Kostaive, discuss the following with your healthcare provider:

• Anxiety-related reactions: Anxiety-related reactions, including vasovagal syncope (fainting), hyperventilation, and stress-related responses, can occur in association with vaccination as a psychogenic response to any needle injection. This can be accompanied by several neurological signs such as transient visual disturbance, paraesthesia, and tonic-clonic limb movements during recovery. It is important that precautions are in place to avoid injury from fainting.
• Bleeding disorders: As with other intramuscular injections, Kostaive should be given with caution to individuals receiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder (such as haemophilia). Bleeding or bruising may occur following intramuscular injection in these individuals. Subcutaneous injection may be considered in exceptional circumstances for individuals with contraindications to intramuscular injection.
• Immunocompromised individuals: The efficacy, safety, and immunogenicity of Kostaive have not been specifically evaluated in immunocompromised individuals, including those receiving immunosuppressive therapy. The immune response to Kostaive may be reduced in immunocompromised persons. The decision to vaccinate should be made on an individual basis, weighing the potential benefits against the potential risks.
• Febrile illness: Vaccination should be postponed in individuals suffering from an acute severe febrile illness or acute infection. The presence of a minor infection or low-grade fever should not delay vaccination.
• Protection limitations: As with all vaccines, vaccination with Kostaive may not protect all recipients. The duration of protection afforded by the vaccine is not yet fully established. Individuals may not be fully protected until 14 days after the second dose of the primary vaccination course or 14 days after a booster dose.

Pregnancy and Breastfeeding

There is limited experience with the use of Kostaive during pregnancy. Animal reproductive toxicity studies have not been completed for zapomeran specifically. As a precautionary measure, vaccination with Kostaive during pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and the developing foetus. This assessment should be made in consultation with a healthcare provider, taking into account national recommendations and the individual’s risk of exposure to SARS-CoV-2 and risk of severe COVID-19.

It is not known whether zapomeran is excreted in human breast milk. A risk to newborns and infants cannot be completely excluded. However, based on the general understanding of mRNA vaccine technology and the rapid degradation of mRNA molecules, the vaccine is considered compatible with breastfeeding. The World Health Organization recommends that COVID-19 vaccination should not be withheld from breastfeeding women if they are otherwise eligible for vaccination. Discuss the decision to breastfeed during or after Kostaive vaccination with your healthcare provider.

Driving and Operating Machinery

Kostaive has no or negligible direct influence on the ability to drive and use machines. However, some side effects such as fatigue, dizziness, and headache may temporarily affect the ability to drive or operate machinery. If you experience these symptoms after vaccination, wait until they resolve before driving or operating heavy machinery.

How Does Kostaive Interact with Other Drugs?

As a vaccine rather than a traditional pharmaceutical drug, Kostaive has a fundamentally different interaction profile compared to most medications. The active substance, zapomeran, is a self-amplifying mRNA molecule encapsulated in lipid nanoparticles. It does not undergo hepatic metabolism via cytochrome P450 enzymes and is not expected to interact with other medications through conventional pharmacokinetic pathways. The mRNA is degraded by normal cellular mechanisms (intracellular ribonucleases) after translation into the spike protein.

No formal drug interaction studies have been conducted with Kostaive. Based on the mechanism of action and the nature of mRNA vaccines, clinically significant pharmacokinetic drug interactions are not anticipated. However, several important considerations apply:

An important practical consideration is that Kostaive must not be mixed with other vaccines or medicinal products in the same syringe or vial. After reconstitution with 0.9% sodium chloride solution, only the resulting vaccine suspension should be drawn from the vial. If other vaccines are being administered at the same visit, they should be given at different injection sites, ideally in different limbs.

For individuals receiving anticoagulant therapy (such as warfarin, heparin, or direct oral anticoagulants like apixaban or rivarelbaan), the intramuscular injection can still be given. Healthcare providers should use a fine needle (23 gauge or thinner) and apply firm pressure to the injection site without rubbing for at least 2 minutes to minimise the risk of haematoma formation.

Individuals receiving immunosuppressive therapy – including high-dose corticosteroids, biological agents (such as TNF inhibitors, rituximab, or other B-cell depleting therapies), chemotherapy, or anti-rejection medications after organ transplantation – may have a diminished immune response to Kostaive. However, vaccination is still recommended in these individuals, as even a reduced immune response may provide some degree of protection. The optimal timing of vaccination in relation to immunosuppressive treatment cycles should be discussed with the treating physician.

What Is the Correct Dosage of Kostaive?

Kostaive should always be administered by a healthcare professional in a setting where appropriate medical treatment for anaphylaxis is immediately available. The vaccine is not intended for self-administration. The following dosage information is based on the European Medicines Agency (EMA) approved Summary of Product Characteristics.

Adults (18 Years and Older)

The vaccine is administered as an intramuscular injection, preferably into the deltoid muscle of the upper arm. The injection must not be given intravascularly (into a blood vessel), subcutaneously (under the skin), or intradermally (into the skin). For individuals with bleeding disorders or on anticoagulant therapy, subcutaneous injection may be considered as an alternative in exceptional circumstances, although the intramuscular route remains the preferred method of administration.

Reconstitution and Preparation

Kostaive is supplied as a white to off-white lyophilised (freeze-dried) powder in a multi-dose vial. Before administration, the powder must be reconstituted with 10 mL of sterile 0.9% sodium chloride (normal saline) solution. Each reconstituted vial yields approximately 16 doses of 0.5 mL. The reconstitution process is performed by trained healthcare professionals as follows:

1. Allow to thaw: If the vial is stored frozen, allow it to thaw at room temperature (up to 25°C) or in a refrigerator (2–8°C). Do not use a microwave or hot water to accelerate thawing.
2. Reconstitute: Using aseptic technique, inject 10 mL of sterile 0.9% sodium chloride solution into the vial containing the lyophilised powder.
3. Mix gently: Swirl the vial gently in a circular motion. Do not shake vigorously, as this may damage the lipid nanoparticles and compromise vaccine integrity.
4. Inspect: The reconstituted vaccine should appear as a white to off-white opalescent suspension. Do not use if the suspension is discoloured or contains visible particles that do not disperse upon gentle swirling.
5. Draw dose: Using a sterile needle and syringe, withdraw 0.5 mL of the reconstituted vaccine for each dose.
6. Administer promptly: After reconstitution, the vaccine must be used within 6 hours when stored at 2–25°C. Discard any unused vaccine after this time.

Children and Adolescents

The safety and efficacy of Kostaive have not been established in children and adolescents under 18 years of age. No data are currently available, and the vaccine is not recommended for use in this age group. Paediatric clinical studies may be conducted in the future to evaluate potential use in younger age groups.

Elderly Patients

No dose adjustment is required for elderly patients (aged 60 years and older). Clinical trials included a substantial proportion of older adults, and no overall differences in safety or immunogenicity were observed compared with younger adults. The immune response in elderly individuals may be somewhat lower than in younger adults, which is a general characteristic of vaccines in older age groups. Despite this, vaccination remains strongly recommended for elderly individuals, who are at higher risk of severe COVID-19 outcomes.

Missed Dose

If you miss the second dose of the primary vaccination course, it should be administered as soon as possible. There is no need to restart the vaccination series. The recommended interval between the first and second dose is 28 days, but if this interval is exceeded, the second dose should still be given. There is no maximum interval for the second dose; however, for optimal protection, the course should be completed in a timely manner.

Overdose

No cases of overdose with Kostaive have been reported in clinical trials. In the event of an overdose (administration of a higher volume or concentration than intended), the recipient should be monitored closely for any adverse effects, and supportive treatment should be provided as clinically indicated. Given the nature of the vaccine, a single overdose is unlikely to cause serious harm, but the recipient should be observed for an extended period and any reactions reported to the relevant pharmacovigilance authority.

What Are the Side Effects of Kostaive?

Like all vaccines, Kostaive can cause side effects, although not everyone who receives it will experience them. The side effects observed during clinical trials and post-marketing surveillance are typical of immune-activating vaccines and generally reflect the body’s normal immune response to the vaccine antigens. The majority of adverse reactions are mild to moderate in intensity and resolve spontaneously within a few days without the need for specific medical treatment.

Clinical trial data from the phase I/II and phase III studies (including the ARCT-154 programme), as well as post-authorisation pharmacovigilance from Japan (where the vaccine has been in use since late 2023), form the basis of the known safety profile. In the pivotal studies, local and systemic reactions were generally reported more frequently after the first dose than after subsequent doses.

Injection site reactions are the most frequently reported local side effects. Pain and tenderness at the injection site are very common and typically develop within the first 24 hours after vaccination. These local reactions are generally mild and short-lived, resolving within 1–3 days. Applying a cool, damp cloth to the injection site and gentle movement of the arm can help relieve discomfort.

Systemic reactions – including fatigue, headache, myalgia, arthralgia, chills, and fever – are also very common, reflecting the activation of the immune system. Fever, when it occurs, typically develops within the first 24–48 hours and resolves within 1–2 days. Paracetamol (acetaminophen) or ibuprofen can be used to manage fever and pain after vaccination if needed. Prophylactic use of antipyretics before vaccination is not routinely recommended, as it may potentially reduce the immune response.

Myocarditis and pericarditis are recognised as a class effect of mRNA COVID-19 vaccines, based on extensive post-marketing experience with other approved mRNA vaccines. These conditions typically present within 14 days of vaccination, more commonly after the second dose, and are observed more frequently in younger males (particularly those aged 18–30 years). Symptoms include chest pain, shortness of breath, and palpitations. Most cases are mild and resolve with conservative management (rest and anti-inflammatory medication), though hospitalisation may be required for monitoring.

Long-term safety data from Japan, where Kostaive has been in use since November 2023, has been reassuring. Post-marketing surveillance has not identified any new safety signals beyond those observed in clinical trials and known class effects of mRNA vaccines. Pharmacovigilance continues as part of the conditions of the marketing authorisation in all approved jurisdictions.

How Should You Store Kostaive?

Proper storage of Kostaive is essential to maintain the integrity, potency, and safety of the vaccine. As a biological product containing mRNA encapsulated in lipid nanoparticles, zapomeran is sensitive to temperature, light, and physical agitation. The following storage guidelines are based on the approved Summary of Product Characteristics and must be strictly followed by healthcare facilities handling the vaccine.

• Long-term frozen storage: Store unopened vials at -15°C to -25°C (5°F to -13°F) for up to 24 months (2 years). Keep vials in the original carton to protect from light. This is the primary storage condition.
• Thawing: Before reconstitution, allow the vial to thaw. Vials can be thawed at room temperature (up to 25°C) or in a refrigerator (2–8°C). Do not use a microwave or warm water bath to accelerate thawing.
• Pre-reconstitution room temperature: Once thawed or removed from frozen storage, the unreconstituted vial can be kept at room temperature (up to 25°C) for a maximum of 4 hours before reconstitution.
• After reconstitution: Once reconstituted with 10 mL of sterile 0.9% sodium chloride solution, the vaccine must be used within 6 hours. During this period, the reconstituted vaccine should be stored at 2°C to 25°C. Discard any unused vaccine after 6 hours.
• Do not refreeze: Once thawed, the vaccine must not be refrozen under any circumstances. Refreezing can damage the lipid nanoparticle structure and render the vaccine ineffective.
• Protect from light: Store the vials in the original carton at all times until ready for use to protect from light exposure.
• Check expiration date: Do not use Kostaive after the expiration date printed on the vial label and outer carton after “EXP.” The expiration date refers to the last day of that month.
• Inspect before use: After reconstitution, visually inspect the vaccine. It should appear as a white to off-white opalescent suspension. Do not use if it is discoloured or contains particulate matter that does not disperse upon gentle swirling.

Unlike some conventional mRNA vaccines that require ultra-cold storage at -60°C to -80°C, Kostaive’s storage requirements at -15°C to -25°C are significantly more practical. Standard pharmaceutical freezers operating at -20°C are adequate, which greatly simplifies the logistics of vaccine distribution, particularly in resource-limited settings or regions with limited ultra-cold chain infrastructure. The lyophilised (freeze-dried) formulation also contributes to improved stability compared to liquid mRNA vaccine formulations.

What Does Kostaive Contain?

Understanding what your vaccine contains is important, particularly if you have known allergies or sensitivities to pharmaceutical ingredients. Below is a detailed breakdown of the composition of Kostaive.

Active Ingredient

The active substance is zapomeran, a self-amplifying messenger RNA (sa-mRNA) that encodes two key elements: the prefusion-stabilised SARS-CoV-2 spike glycoprotein (S protein, G clade, D614G variant, with inactivated furin cleavage site) and a replicase enzyme derived from the Venezuelan equine encephalitis virus (VEEV) replicon. The sa-mRNA is encapsulated in Arcturus Therapeutics’ proprietary LUNAR (Lipid-enabled and Unlocked Nucleomonomer Agent modified RNA) lipid nanoparticles. Each reconstituted dose (0.5 mL) contains 5 micrograms of zapomeran.

Inactive Ingredients (Excipients)

Appearance and Pack Sizes

Kostaive is supplied as a white to off-white lyophilised powder in a multi-dose glass vial sealed with a rubber stopper and aluminium flip-off cap. Each vial is reconstituted with 10 mL of sterile 0.9% sodium chloride solution to yield approximately 16 doses of 0.5 mL each. The vaccine is available in packs as specified by the marketing authorisation holder. Not all pack sizes may be marketed in every country.

The reconstitution diluent (0.9% sodium chloride for injection) is not included in the vaccine pack and must be sourced separately by the healthcare facility. Only sterile, preservative-free 0.9% sodium chloride solution should be used for reconstitution.

Marketing Authorisation Holder and Manufacturer

The marketing authorisation holder for the European Union is Arcturus Therapeutics Europe B.V., based in the Netherlands. The vaccine is manufactured by Seqirus Netherlands B.V., Amsterdam. The global commercialisation partner is CSL Seqirus (part of CSL Limited, Australia), one of the world’s largest influenza vaccine providers. In Japan, Kostaive is marketed and distributed by Meiji Seika Pharma Co., Ltd. The self-amplifying mRNA technology (STARR™ platform) and LUNAR™ lipid nanoparticle delivery system were developed by Arcturus Therapeutics, Inc. (San Diego, USA).